This Article Figures Only Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Fisher, N. G. Articles by Lindner, J. R. Search for Related Content PubMed PubMed Citation Articles by Fisher, N. G. Articles by Lindner, J. R.

EXPERIMENTAL STUDY

Influence of microbubble surface charge on capillary transit and myocardial contrast enhancement

^* Cardiovascular Imaging Center, Cardiovascular Division, University of Virginia, Charlottesville, Virginia, USA

Manuscript received January 4, 2002; revised manuscript received April 4, 2002, accepted May 7, 2002.

^* Reprint requests and correspondence: Dr. Jonathan R. Lindner, Cardiovascular Division, Box 800158, Medical Center, University of Virginia, Charlottesville, Virginia 22908-0158, USA.
jlindner{at}virginia.edu

OBJECTIVE: The goal of the study was to determine whether microbubble charge influences the microvascular retention of microbubble contrast agents.

BACKGROUND: Interactions between serum proteins and lipid membranes are greater with anionic compared with neutral membranes. These interactions may influence the microvascular behavior of anionic lipid microbubbles.

METHODS: Intravital microscopy of the cremaster muscle was performed in six wild-type mice and three C3-deficient mice during intravenous injection of lipid-shelled microbubbles with either a neutral or a negative charge. Both agents were prepared with and without a protective surface layer of polyethyleneglycol (PEG). Complement attachment to microbubbles was assessed by flow cytometry with flourescein isothiocyanate-conjugated anti-C3b monoclonal antibody. Myocardial contrast echocardiography was performed in six dogs to assess pulmonary and myocardial retention of microbubbles.

RESULTS: Size-independent capillary retention of microbubbles, occurring for a few seconds to >10 min, was frequently observed with anionic, but rarely with neutral, microbubbles (4.3 ± 0.3 vs. 0.4 ± 0.1 mm^–3, p < 0.01). Anionic microbubble retention was reduced by 70% by surface PEG and was also markedly reduced in C3-deficient mice (1.4 ± 0.1 mm^–3, p < 0.05 vs. wild-type). Flow cytometry demonstrated complement attachment to only anionic microbubbles. Contrast echocardiography indicated both pulmonary and myocardial retention of only anionic microbubbles, the latter evidenced by persistent opacification >10 min after bolus intravenous injection.

CONCLUSIONS: Lipid microbubbles with a net negative charge can be retained within capillaries via complement-mediated attachment to endothelium. This property may be useful for the development of ultrasound contrast agents that can be imaged late after venous injection.

Abbreviations and Acronyms   C3–/–   C3-deficient   FITC   fluorescein isothiocyanate   LV   left ventricular   mAb   monoclonal antibody   MBneg   lipid microbubbles with a net negative charge   MBneut   lipid microbubbles with a net neutral charge   PEG   polyetheleneglycol   PEG–   without a surface polyetheleneglycol layer   PEG+   with a surface polyetheleneglycol layer   RV   right ventricular   VI   video intensity

This article has been cited by other articles:

				D. R. Anderson, J. M. Tsutsui, F. Xie, S. J. Radio, and T. R. Porter The role of complement in the adherence of microbubbles to dysfunctional arterial endothelium and atherosclerotic plaque Cardiovasc Res, February 1, 2007; 73(3): 597 - 606. [Abstract] [Full Text] [PDF]

				M. Braide, H. Rasmussen, A. Albrektsson, and U. Bagge Microvascular behavior and effects of sonazoid microbubbles in the cremaster muscle of rats after local administration. J. Ultrasound Med., July 1, 2006; 25(7): 883 - 890. [Abstract] [Full Text] [PDF]

				J. Yoshida, K. Ohmori, H. Takeuchi, K. Shinomiya, T. Namba, I. Kondo, H. Kiyomoto, and M. Kohno Treatment of Ischemic Limbs Based on Local Recruitment of Vascular Endothelial Growth Factor-Producing Inflammatory Cells With Ultrasonic Microbubble Destruction J. Am. Coll. Cardiol., September 6, 2005; 46(5): 899 - 905. [Abstract] [Full Text] [PDF]

				J. M. Tsutsui, F. Xie, M. Cano, J. Chomas, P. Phillips, S. J. Radio, J. Lof, and T. R. Porter Detection of retained microbubbles in carotid arteries with real-time low mechanical index imaging in the setting of endothelial dysfunction J. Am. Coll. Cardiol., September 1, 2004; 44(5): 1036 - 1046. [Abstract] [Full Text] [PDF]

				H. Kunichika, B. Peters, B. Cotter, H. Masugata, N. Kunichika, P. L. Wolf, and A. N. DeMaria Visualization of risk-area myocardium as a high-intensity, hyperenhanced "hot spot" by myocardial contrast echocardiography following coronary reperfusion: Quantitative analysis J. Am. Coll. Cardiol., August 6, 2003; 42(3): 552 - 557. [Abstract] [Full Text] [PDF]